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Exosomes from human urine-derived stem cells carry NRF1 to alleviate bladder fibrosis via regulating miR-301b-3p/TGFβR1 pathway

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Abstract

Bladder outlet obstruction (BOO) is a common disease that always make the bladder develops from inflammation to fibrosis. This study was to investigate the effect of exosomes from human urine-derived stem cells (hUSCs) on bladder fibrosis after BOO and the underlying mechanism. The BOO mouse model was established by inserting a transurethral catheter, ligation of periurethral wire, and removal of the catheter. Mouse primary bladder smooth muscle cells (BSMCs) were isolated and treated with TGFβ1 to mimic the bladder fibrosis model in vitro. Exosomes from hUSCs (hUSC-Exos) were injected into the bladder of BOO mice and added into the culture of TGFβ1-induced BSMCs. The associated factors in mouse bladder tissues and BSMCs were detected. It was confirmed that the treatment of hUSC-Exos alleviated mouse bladder fibrosis and down-regulated fibrotic markers (a-SMA and collagen III) in bladder tissues and TGFβ1-induced BSMCs. Overexpression of NRF1 in hUSC-Exos further improved the effects of hUSC-Exos on bladder fibrosis both in vivo and in vitro. TGFβR1 was a target of NRF1 and miR-301b-3p, and miR-301b-3p was a target of NRF1. It was next characterized that hUSC-Exos carried NRF1 to up-regulate miR-301B-3p, thereby reducing TGFβR1level. Our results illustrated that hUSC-Exos carried NRF1 to alleviate bladder fibrosis through regulating miR-301b-3p/TGFβR1 pathway.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the Project of Henan Medical Science and Technology in 2018 (Grant Nos. 2018020023, 2018020141), and the National Natural Science Foundation of China (Grant No. 81901974).

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Author notes

  1. Junwei Wu, Xinxin Wang and Guoping Fu authors contribute equally to the manuscript.

Authors and Affiliations

  1. Department of Urology, The First Affiliated Hospital of Zhengzhou University, Jianshe East Road, No. 1, Zhengzhou, 450052, Henan, China

    Junwei Wu, Yiyuan Feng, Yan Wang, Guoxian Zhang, Yudong Wu, Jianguo Wen & Qingwei Wang

  2. School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China

    Junwei Wu, Xinxin Wang & Lirong Zhang

  3. Hua County People’s Hospital, Anyang, Henan, China

    Junwei Wu, Xinxin Wang, Guoping Fu, Hongyu Meng & Bing Zhang

  4. Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

    Xinxin Wang

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  1. Junwei Wu
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Contributions

JW, BZ and QW put forward the concept of the study, designed the study, prepared the manuscript and contributed to the statistical analysis. XW and GF contributed to the data acquisition and edited the manuscript. YW, GZ and YW contributed to the quality control of data and algorithms. LZ,HM, and JW analyzed the data and interpretation. BZ and QW put forward the concept of the study, contributed to the data analysis and interpretation and reviewed the manuscript. YF contributed to all the major revision of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Bing Zhang or Qingwei Wang.

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Wu, J., Wang, X., Fu, G. et al. Exosomes from human urine-derived stem cells carry NRF1 to alleviate bladder fibrosis via regulating miR-301b-3p/TGFβR1 pathway. Mol Cell Biochem 478, 249–260 (2023). https://doi.org/10.1007/s11010-022-04484-3

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